Rectal insert

ABSTRACT

A method of treating hemorrhoids which comprises inserting into the rectum of a subject afflicted therewith a substantially cylindrical shaped insert, comprising a water swellable polymer having a water content of at least 35% by weight, said insert having previously been frozen by being subjected to a temperature below 0° C. for a sufficient amount of time to freeze the free water therein and maintaining said insert with at least a portion thereof outside the sphincter muscle, and apparatus therefore.

BACKGROUND OF THE INVENTION

The hemorrhoids, or piles, are swollen varicose veins in the mucousmembrane inside or just outside the rectum.

One common cause of piles is constipation and the straining to eliminatehard, dry stool. The excessive pressure causes a fold of the membraneousrectal lining to slip down, thus pinching the veins and irritating them.

Women during pregnancies are particularly subject to the hemorroidalproblem because of the pressure in the veins in the lower body area.

Other causes are diseases of the digestive tract resulting in analinfection, and cirrhosis of the liver, which obstructs blood flow andputs increased pressure on the hemorrhoidal veins.

Once the hemorrhoids are formed, they can further deteriorate or ruptureby additional pressure during constipation and straining at stool, or byexternal pressure by long sitting (particularly if the piles areprolapsed or external).

The ruptured and bleeding piles are sensitive to infection; the swellingcaused by inflamation affects, in turn, the hemorrhoids by pressing theveins.

The hemorrhoidal problems are self-accelerating and the prevention ofthe progressive deterioration of the problem is the essential conditionof a successful treatment.

The treatment methods range from warm bath through ointments andsuppositories to surgery or an injection chemotherapy to controlbleeding and to eliminate the varicose veins. Often several methods arecombined to address various aspects of the disease.

One approach to the treatment is to relieve the pain and to diminish theswelling by cooling of the hemorrhoidal tissue. For instance Cowie inU.S. Pat. No. 969,134 suggested the use of hollow insert filled withcrushed ice or another cooling medium which was refilled for every use.

More recently Harris in U.S. Pat. No. 3,939,842 suggested a plasticrectal insert with encapsulated freezable liquid, preferrably water,equipped with a bulbous collapsible end. Both devices above have severalshortcomings in common:

(1) The surface of the device may have very low temperature so that itcan cause frost-bites to the sensitive rectal tissue. The frost-bitesoccur when the intracellular liquid is frozen, rupturing the cellmembrane. This may happen even at moderately sub-zero temperatures ifthe contact between device and tissue is intimate and heat transferefficient, which is the case for both devices.

(2) Neither of the devices is inherently disposable which can increasethe risk of infection. Although the Harris device is intended to bedisposable, it lacks any features preventing its multiple use. Itspresumably higher cost, if compared with ointments or suppositories, mayencourage its multiple use.

(3) Both devices have one single function, the cooling of the tissue inthe rectal canal. This treatment has to be combined with other means,such as ointments, lubricants or suppositories etc., which support thetreatment and the discomfort relief by delivering certain drugs,protective and lubricating layer onto the swollen tissue and by eventualsoftening the stool.

(4) Neither device can be applied without a lubricant.

Therefore, the freezable liquid encapsulated in a solid shell cannotutilize fully the beneficial cooling effect and introduces certainrisks.

Suppositories cannot be used for the cooling effect because of theirshape: the pressure of the sphincter squeezes them immediately from therectal canal into bottom of the colon. This holds even for hydrogelsuppositories, as described e.g. by Byrne and Aylott in U.S. Pat. No.4,292,300, which could have otherwise sufficient heat capacity due torelatively high water content. The role of suppositories in general isdrug delivery, and their cooling effect in the rectal canal was neversuggested or anticipated. Therefore, suppositories in general differsubstantially from the rectal inserts described either in the prior artor in the present invention.

SUMMARY OF THE INVENTION

It has been found that the free water in a hydrogel containing more than35% by weight of water can be readily frozen by reducing the temperatureof its environment approximately below 0° C., preferably below -5° C. Ithas further been found that such a frozen rigid body has the interestingproperty that as soon as its surface is contacted with skin at or closeto body heat a substantially non-frozen gel film is immediately formedbetween the skin and the frozen portion of the gel. This useful propertymay be utilized in the treatment of hemorrhoids with or without thecontemporaneous delivery of pharmaceutically active materials into themucosa of the rectum.

The present invention provides a rectal insert made of frozen hydrogel,a method of making same and a method of using the same.

In its simplest form the invention comprises a substantially cylindricalinsert of frozen hydrogel having a substantially conical nose portionfor insertion into the rectum and a collar of substantially greaterdiameter than the main portion of the insert placed proximate to therear end of the insert, said collar acting as a block to insertion ofthe device entirely through the sphincter muscle. This property permitsapplication of reduced temperature to most of the areas liable to beeffected by hemorrhoids.

Numerous different embodiments of this invention are discussed infurther detail hereinbelow including especially means for permitting thedevice to be held in position by the sphincter muscle itself afterinsertion and not expelled as would be the natural tendency of action ofsaid sphincter muscle and its adjacent musculature.

The device is provided in the form of a disposable "bubble type" packagewherein the hydrogel is provided in gel form to the space provided bythe bubble which is in the shape of the desired form of the rectalinsert.

Prior to use the entire package is cooled, suitably by placing it in thefreezer compartment of a domestic freezer. The package is then openedwhereby, in the preferred embodiment the two halves of the bubble packare separated to provide the frozen insert. The insert is then removedand inserted into the rectum of the afflicted subject. Where thesimplest embodiment of the invention is utilized the muscle system ofthe rectum will tend to expel the insert unless the subject, afterinsertion, lies substantially flat on his stomach which would permit himto retain the device in place. The choice of the male pronoun isdeliberate and not accidental since it has been found, surprisingly,that while male test subjects are not able to retain the insert in asitting position, i.e. on a toilet, female test subjects have been ableto do so without great difficulty.

The preferred embodiment having a further substantiallyfrustro-conically shaped forward collar may be inserted while thesubject is in the sitting position and will be retained because of theinteraction of the rearward portion of the said collar with the internalface of the sphincter muscle.

The device is left in place for between 1 to 5 minutes after which timeit may either be removed, or left in place until the combined action ofbody heat and pressure of the sphincter muscle dissolves that portion ofthe insert upon which it acts causing any undissolved portion of theinsert, internal of the sphincter muscle to be retained and permitted tomove up into the colon.

The hydrogels themselves which are utilized in the formation of therectal insertions of the present invention are entirely withoutphysiological effect and the thus produced gels, sols, or solutionsthereof may be retained in the colon until the next bowel movementwithout any adverse physiological effect.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a plan view of the preferred embodiment of the rectal insertof the present invention.

FIG. 2 is a plan view of a package for another embodiment of the presentinvention.

FIG. 3 is a side cross-sectional elevational view of a package for theembodiment of FIG. 1.

FIG. 4 is an axial cross-sectional view of the embodiment of FIG. 1viewed from 4--4 showing a particular improvement thereon.

FIG. 5 is a simple embodiment of the rectal insert of the presentinvention.

FIG. 6 is another embodiment of the rectal insert of the presentinvention especially suited for the use thereof for drug delivery.

FIG. 7 is a perspective plan view of an embodiment of a presentinvention comprising a handle and collapsible insert filled withhydrogel.

FIG. 8 is a plan view of a package comprising yet another embodiment ofthe invention wherein the insert portion comprises the hydrogel segmentand a substantially rigid combined carrier and blocking portiontherefore.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The rectal insert of the present invention is preferably, but notsolely, to be marketed as a blister type package having a blister ofpredetermined form in the form of the rectal insert itself, said blisterbeing filled with a gel comprising a hydrogel polymer and water inproportions more particularly described hereinbelow.

The type of blister pack chosen will depend upon commercialconsiderations as well as the nature of the gel chosen. Gels having awater content of, say, 35-90% can be fairly shape sustaining and can bepacked in packages having very little mold forming effect. Above 90%water the gels, at ambient temperature, are not form retaining. Thesegels can be retained either in a preformed substantially rigid blisterpack made of, say, PVC or polystyrene. Alternately, "soft" blister packsof polyethylene may be used into which the gel is injected undermoderate pressure, if desired by softening the pack with heat.

Prior to use the package is cooled below the freezing point of water. Atemperature reduction to -5° C. is generally suitable though anydomestic freezer, which has temperatures down to about -15° C. may alsobe employed.

It is an special advantage of the present invention that such furtherreduction in temperature carries no adverse effect such as frostbiteduring use.

This advantage arise from the special properties of water swellablepolymers suitably hydrogels. When ice is contacted with a warm surface,such as skin, the top surface is melted to water which on application ofpressure as will occur in the rectum, will be pushed away permitting theskin to contact the ice itself thus giving rise to frostbite. Incontrast when a gel is frozen there is a phase separation of ice andgel. When the upper layer of ice is melted the water thus liberatedremains in the gel, forming a layer whose temperature will not fallbelow 0° C. and at the same time prevents contact with the inner frozensurface. While the rectal insert could be either fluid or self formsustaining at ambient temperatures, the discussions which follow aredirected to a description thereof in the frozen form.

In the use of the rectal insert in the treatment of hemorrhoids, (towhich use the device is by no means limited as will be discussed infurther detail hereinbelow) it is important to maintain contact betweenthe cooling surface and the hemorrhoidal tissue for as long a period oftime as possible. It has generally been accepted in the art that aminimum treatment time of 1 minute is essential while it would bedesirable to increase the contact time up to approximately 5 minutes ormore.

It is an important consideration in this treatment that hemorrhoidalveins occur in the area of the rectum itself in and around the sphinctermuscle and outside the sphincter muscle. A successful device musttherefore maintain contact in all areas. Thus, a device shaped in theform of a conventional suppository which will readily travel through thesphincter muscle and then up into the colon while satisfactory forchemical treatments of hemorrhoids is unsatisfactory for thermaltreatment as the contact time is too short.

The simplest device is illustrated as insert 500 in FIG. 5. Rectalinsert 500 comprises a substantially cylindrical central shaft portion510 having a substantially conical nose portion 512 and a stopperportion 530 having a forward surface 532. The device is used byinserting nose section 512 through the sphincter muscle of the rectum upto the point where surface 532 contacts the outside of said sphinctermuscle. The insert is left in place until either it melts completely oris removed after a sufficient length of time has passed.

The general pressures generated by the sphincter muscle and adjacentmuscles of the rectum when the subject is in the seated position tend toexpel all inserted bodies. Thus, where the embodiment of FIG. 5 isemployed it would be necessary to maintain constant inward pressure onthe device which may be considered inconvenient and somewhat unesthetic.Alternatively, the device maybe readily inserted and maintained inposition when the subject is lying face down on a bed. Even in thissituation there are esthetic disadvantages because of the neccessity ofprotecting the bed against the melting insert by towels and the like.Nevertheless, despite the foregoing disadvantages this simple embodimentis operative.

The preferred embodiment of the invention is that illustrated in FIG. 1with the improvement illustrated in FIG. 4.

This embodiment comprises, in the frozen state, a rectal insert 100having a substantially cylindrical portion 110 provided with asubstantially conical nose portion 112. Rearwardly of section 110 isprovided a collar section 114 which, most desirably, is provided with asubstantially frustro conical cross-sectioned forward face 114 tofacilitate passage of the collar thru the sphincter muscle and arearward face 118 to reduce the likelihood of the device, once inserted,being expelled outwardly through the sphincter. Rearwardly of collar 116is substantially cylindrical mid-section 120. Rearward of this section120 is provided a rearward collar 130 having a forward buffer face 132and a rearward face 134. It is not essential that collar 130 entirelygirdle the device since its sole purpose is to act as a stopperpreventing the passage of the entire device through the sphinctermuscle. Nevertheless, it is both simple to provide for 130 to entirelygirdle the device and furthermore, such construction substantiallystrengthens collar 130.

Rearward of stopper 130 is holding section 140. The presence of thisadditional section is a matter of mere convenience and is in no wayessential to the operation of the device. Numerous conveniences can beincorporated thereon, if desired, for example, as illustrated in FIG. 4,two of the sides of 140 can be shaved to the substantially mutuallyparallel arrangements 142 illustrated which would make it easier to holdthe device between two fingers when inserting the same or removing thesame. Similarly, a holding means of cloth, plastic, wood, or othermaterials may be incorporated into sector 140 and protruding therefromto provide a drier surface for handling during insertion or removal.Again these are a matter of convenience and do not affect the essentialoperation of the device. It is contemplated that after insertion thefrozen hydrogel will melt, thus reducing the external dimensions of thedevice including but not limited to, forward collar 116 to the point atwhich the device will either to auto-expelled by the sphincter musclewhen the subject is in the sitting position or the dimensions will be soreduced that the device can readily be withdrawn outwardly through thesphincter muscle.

Nevertheless, there are circumstances wherein it would be desirable tomaintain the entire segment of the insert forward of sector 120 insidethe rectum and, after substantial completion of the cooling effect bepermitted to travel up the colon in the manner of a conventionalsuppository.

This embodiment is particularly preferred when the treatment calls forthe additional delivery of a pharmaceutically acceptable amount of arectally administrable pharmaceutically active compound. One form ofthis embodiment is illustrated in FIG. 6 which has some of thecharacteristics of FIG. 1 device and some of those of FIG. 5 device.Particularly to be noted, however, in device 600 of FIG. 6 is a verysubstantial narrowing of mid-section 620 so that its diameter is between25 and 75% that of, say, forward shaft portion 110. Needless to say thesphincter will rest within this indentation and exert excess pressurethereon to the point at which this segment will melt and break prior tothe melting of the forward segments of the insert causing the insert tobe propelled up into the colon as mentioned hereinbefore. In anunillustrated modification of this embodiment forward collar 614 isomitted.

As mentioned heretofore at ambient temperatures the device may be in agel form which is not or substantially not self retentive of form. Sinceit is convenient to package it in this manner and it is unnecessary tomaintain a device in the frozen state except just prior to use, it isconvenient to employ any disposable type of blister packaging. It is,however, particularly advantageous to utilize heat formable sheets ofthermo plastic material. One modification of such packaging isillustrated in FIGS. 2 and 3. The packaging 256 comprises a pair ofpre-shaped blister sheets 254 and (not illustrated) 252. These aresealed around the edges thereof by thermal bead seal 256. In manufactureof the device the gel material is injected into space 210 byconventional means through orifice 250 after which the seal iscompleted.

In order to facilitate opening of the package there may, optionally, beprovided assisting means such as notch 254 and score line 262. It willbe noted that as described above, the flat portion of package 256 isonly sealed together at the edge. While such otherwise unsealed contactis not an essential part of the invention and these flat portions may besealed together, for example, by heat sealing, leaving them unsealedsubstantially facilitates opening of the device. Thus, it will be clearto those skilled in the art that the actual location of the heat seal256 although illustrated as a circumferential bead seal may be locatedat other places on the packaging as long as it is circumferential to thelocation of the gel matter itself. Indeed as mentioned above where"soft" packaging is employed for a gel in substantially fluid form atambient temperature, the circumferential seal should actually outlinethe shape of the insert.

The embodiment of FIG. 7 comprises a handle portion 730 and a tubularportion 710 having a multiplicity of orifices 711 therein. The aforesaidcombined article comprising segments 710 and 730 may be made of any softcollapsible material including but not limited to multiblock co-polymerhydrogel of acrylonitrile and acrylamide having an equilibrium swellingof 73% with water. Such a hydrogel polymer is recommended because ofcheapness but other polymers or rubbers may also be employed.

This portion of the device is placed in a mold similar to that depictedin FIGS. 2 and 3 and the hydrogel suitably a hydrogel comprising morethan 90% by weight of water is injected into the mold so that entiresection 710 is filled therewith. After freezing in the usual manner, thedevice is inserted in the usual manner.

While the device of this embodiment may either be used in the subjectface down position or else hand held for a subject in the sittingposition, the form of the handle will tend to eliminate many of theesthetic problems of, say, the device of FIG. 5. As the inserted portionof the device becomes warmer the combination of melting and pressure ofthe rectal muscles will force the gel out of the orifices 711 and, aftera predetermined time, the device can be withdrawn and discarded. Thisparticularly form of device is well suited for the contemporaneousadministration of pharmacologically active agents which are to beadministered rectally, and due to its design there is no possibilitythat an attempt would be made to recharge or re-use the remainingcarrier portion after one employment.

FIG. 8 illustrates yet another embodiment of the invention wherein thehandling portion and the rearward collar portion are made of materialsother than hydrogel. In this embodiment the package comprises the usualblister pack 854/852 sealed by circumferential heat seal 856. Within thebubble there is provided a rearward portion comprising the handlesegment 840 and the rearward collar section 830. For reasons ofstability in use, a longitudinal protrusion 836 having a small bar orplug 835 attached thereto perpendicular to the longitudinal axis, servesto avoid the premature separation of the gel portion of the insert fromthe handle portion.

The hydrogel is introduced through orifice 850 in pack 854 which issubsequently sealed in the conventional manner.

While the embodiment of FIG. 8 does not illustrate a forward collar suchas that shown as item 114 in FIG. 1, such a forward collar could readilybe incorporated but would, suitably, be of frozen hydrogel. The insertof FIG. 8 is utilized in a similar manner to that of FIGS. 2, 5 and 7.The use of a non-hydrogel handle and rearward collar is more desirableesthetically but tends to raise the cost of the insert not only becauseof the cost of the materials involved but because of the necessity ofseveral additional manufacturing steps including but not limiting to theactual manufacture of the handle portion and its insertion into thepackage prior to the injection of the hydrogel.

The hydrogel rectal insertion of the present invention comprises

(a) an essentially cylindrical stem of diameter about 5 to 15 mm and oflength 35 to 125 mm, made of hydrogel having equilibrium water contenthigher than about 35% preferably over 90% most suitably 95-99% by weightand a substantial part of the swelling water freezing between -1 and +1deg. C., which stem is to be inserted into the rectum in frozen state;and desirably,

(b) a non-insertable end which adheres firmly to the said stem at leastin its frozen state. While this non-insertable end may, as describedabove, comprise a hydrogel collar, the invention is not so limited andit may be made of any rigid material such as wood, plastic or cardboard.

The hydrogel mentioned above is a crosslinked or non-crosslinked polymerwhich swells in water to a certain equilibrium water content but iswater-insoluble at ambient or body temperature. The equilibrium watercontent at ambient temperature is at least 35% by weight, based onswollen hydrogel; and a substantial part of the swelling water is in afree state, being crystallizable in the same manner as water itself.Thus, an essential feature of the hydrogel used in present invention isits content of water in two states--hydration water (which does notfreeze) and free water freezes close to 0° C. The hydrogels usable inour invention contain a substantial proportion of water crystallizableat near sub-zero temperatures, while the remaining part of the waterserves to hydrates the polymer molecule. (for more details on free, ormobile, and bound water phases in hydrogels see e.g. Andronikashvili etal,: Biopolymers, 1976, 15, 1991).

The mobile water phase has the following major funtions: it contributessubstantially to heat capacity of the system and it assures thattemperature of the molten outer layer of hydrogel is close to, but notbelow 0° C.

The bound water plasticizes the polymer which would otherwise be brittle(mixture of ice crystals and non-plasticized polymer would be as brittleas or even more brittle than ice itself).

Although certain hydrogels can have as little as 35% of swelling waterto be useful in the present invention, the hydrogels with water contentover 70% of water are preferred. At this water content the mobile waterdistinctly prevails over the bound water even if the gel is homogeneous.The mobile water consists of cage-like structures which cannot be fullydeveloped if the pores or intermolecular spaces are smaller than about40 to 50 ° A. The percentage of such small spaces decreases withswelling capacity, and at about 70% of water the volume of the largepores prevails even for hydrogels with large inherent binding capacity.

We have found that the freezing characteristics of some hydrogels withswelling capacity between 35 and about 70% of water depend, to someextent, on conditions of their preparation, thermal history, etc. Thehydrogels with higher water content than about 70% are, on the otherhand, only very slightly sensitive to those factors. Moreover, both heatcapacity and thermal conductivity increase with increasing water contentat a substantially exponential rather than linear rate, and above about70% of water the contribution of the mobile water to the thermodynamiccharacteristics starts to prevail over the contributions of the boundwater and the polymer in readily predictable way.

Basically any polymer swelling capacity of over 70% of water can be usedin the present invention. Examples of such polymers are polymers andcopolymers of acrylamide, methacrylamide, and their N-substitutedderivatives; polymers and copolymers of acrylic, methacrylic, maleic anditaconic acids; polymers and copolymers of hydrophilic esters of acrylicand methacrylic acid, such as 2-hydroxyethylmethacrylate,glycerylacrylate and similarly; polymers and copolymers of vinylpyrridine, or vinylpyrrolidone; polycondensates of polyethers, such aspoly(ethylene) or poly(propylene)glycos and their graft or blockcopolymers; polysaccharides, such as starch; cellulose and itsderivatives, such as methylcellulose; polypeptides, such as collagen orelastin or gelatin; and mixtures containing a substantial portion ofsuch hydrophilic polymers.

The said hydrogels can be covalently cross-linked in the manner wellknown per se, e.g. by copolymerization with bifunctional copolymers, byaldehydes or by irradiation, depending on the polymer type.

The non-crosslinked, though water-insoluble hydrogels are preferredbecause of their better processing characteristics in general.

Particularly preferred hydrogels are those derived frompoly(acrylonitrile) and containing amidic and/or carboxylic functionalgroups. There are several classes of such hydrogels. One of themcontains block copolymers of acrylonitrile, as described e.g. in U.S.Pat. No. 4,337,327.

The other class are acrylonitrile-grafted and subsequently hydrolyzedpolysacharides, such as starch. This type of hydrogels has beendescribed in numerous papers, such as M. O. Weaver et al., Journal ofApplied Polymer Science, Vol. 15, pp. 3015-3024 (1971). Similarcopolymers can be prepared by direct grafting of acrylamide onto starch,as described e.g. by G. F. Fanta et al., Journal of Applied PolymerScience Vol. 16, 2835-2845 (1972). The above mentioned hydrogels canform hydrogels with very low content of solids and with very highcontent of freezable water. The hydrogels are very soft in the moltenstate and they have lubricating properties.

We found it advantageous if a major part of the insert is formed from ahydrogel with water content higher than 90% and preferably higher than98% of water which has following properties:

(1) it is strong enough in molten state between 0° and 50° C. to retainits integrity in a plastic wrapping foil, but it disintegrates under thepressure of the sphincter muscle, when molten, to a lubricating Jelly;

(2) its swelling capacity in water strongly increases with temperature;

(3) it can be molten in presence of water at a temperature between about50° and 105° C. Examples of such hydrogels are multiblock copolymers ofacrylonitrile-acrylamide with water content between about 95 and 99.7%of water; gelatine with water; starch gels; and the mixtures thereof.

There are several advantages of the use of the high-water contenthydrogel collapsible by pressure. Firstly, the collapsible hydrogelforms a lubricating (molten) layer on the surface of the frozen insert.Secondly, the collapse of the hydrogel by melting in rectum prevents itsre-use on the one hand, and provides a protective and lubricating layeron the rectal tissue on the other.

Thirdly, the collapse of the molten layer improves heat transfer betweenthe tissue and the frozen core of the insert. Both the tissues and thecore have roughly constant temperature and the collapse of the hydrogelensures that the heat transfer is mediated by a hydrogel layer ofconstant heat conductivity and of constant thickness.

The increasing swelling capacity with temperature causes expulsion ofcertain amount of free water during the melting. The water and theexcess of molten and disintegrated hydrogel are expulsed from rectalchannel into the bottom of the colon, helping to soften excrements andprotect the rectal tissue at stool.

The additional advantage of the collapsible hydrogels is that they stayin the rectum much longer than the insert itself. The cooling functionof the insert lasts several minutes, while the lubricating andmedicating function of hemorroidal suppositories has to last much longerto be effective. Hence, the use of the collapsible hydrogel enables usto combine functions of the cooling insert, suppository and ointment insingle device.

While it is the principal purpose of the present invention to providefor the shrinking of hemorrhoids by reducing the temperature of theirenvironment, it is within the scope of the present invention to utilizethe devices disclosed and claimed herein as drug delivery systems bothas an additional treatment for hemorrhoids or for any other desirablephysiological effect in which there is incorporated in the rectal inserta desired pharmaceutically acceptable amount of any predeterminedrectally administerable pharmaceutically active compound.

When administered the medication can be either dissolved in the waterphase or dispersed in the hydrogel, depending on its solubility inwater. Particularly useful are drugs causing symptomatic relief ofinflamation and swelling such as Dexamethasone, Hydrocortisone,Phenylbutazone or Prednisolone; local anesthetics, such asPhenazopyridine or Procaine; tissue-shrinking drugs, such asPhenylpropanol amine; antibiotics; natural substances used inhemorroidal ointments or suppositories, such as shark-liver oil, yiestcell derivatives and the like. The water-insoluble substances can bedissolved in oily substances (e.g. regular rectal ointment bases) whichare subsequently dispersed in the hydrogel. As long as a major part ofhydrogel is used so that the dispersion is of oil-in-water type, theoily substances do not interfere with the freezing process. On the otherhand, they further improve lubrication and the transport of the drugsinto the tissue. The amount of medication then administered both withrespect to concentration and dosage amount is substantially similar tothat employed in conventional suppositories using those medicaments (seePhysicians Desk Reference, U.S. Pharmacopoea etc.).

EXAMPLES Example 1

40 weight parts (w/w) of 2-hydroxyethyl methacrylate monomer containing0.7% of ethyleneglycol dimethacrylate was mixed with 60 parts (w/w) ofwater and 0.5 parts (w/w) of 30% hydrogen peroxide. The mixture waspolymerized at 65° C. in a polyethylene mold. After the polymerizationwas finished, the mold was opened and the polymerized article was washedthoroughly with water. The spongy hydrogel in the form depicted in FIG.5, having insertable stem 510 with rounded tip 512, and the enlargednon-insertable end portion 530, was packaged in heat-contractableplastic foil. The hydrogel itself contained 60% of water, of which about20% of freezable water was contained in the microscopic pores.

Example 2

Multiblock copolymer hydrogel consisting of acrylonitrile andacrylamide, having an equilibrium swelling 73% of water, wasinjection-molded into a hollow tubular article 710 with multipleorifices 711 and end handle-like portion 732 as depicted in FIG. 7.

1 part (w/w) of powdered copolymer of starch grafted with acrylonitrileand subsequently hydrolyzed by sodium hydroxide), was washed, dried andmixed with 5 parts of (w/w) of potato starch and with 100 parts (w/w) ofwater. The paste was heated to 100° C. to liquify it.

The cavity 713 of the hydrogel article 710 was then filled with the hotliquified paste, which was subsequently gelified by cooling.

The outer wall 715 of the hydrogel article 710 having a water content of73% has lower thermal conductivity than the hydrogel with high watercontent inside, thus prolonging the cooling action. It simultaneouslyprotects the weak gel inside during transport and handling. The moltengel inside the device is disintegrated by rectal pressure and squeezedout of the jacket by the side and end orifices. The outer hydrogeljacket is extracted from the anus after the inner gel becomes molten andis left behind as lubricant and, potentially, as a drug carrier.

Example 3

Polyacrylonitrile of molecular weight 350,000 was dissolved in mixtureof 71% nitric acid and 98% sulfuric acid (9:1 w/w) to form a viscoussolution having 5% of solids (w/w). The solution was allowed to standfor 240 hours so that the nitrile groups were substantially allhydrolyzed, then the solution was poured into excess of cool water sothat the polyacrylonitrile hydrolyzate (PAN) coagulated. The clear softgel with equilibrium swelling over 95% of water was thoroughly washed,dried and ground to a fine powder.

7.5 parts (w/w) of the powdered PAN hydrolyzate was added to 990 parts(w/w) of water and heated to boiling point until the powder dissolved.The solution thus formed was gellified by cooling to ambient temperatureto a clear, soft gel which could be disintegrated by a moderatepressure.

The two part mold is prepared from PVC foil 0.0075" thick as depicted inFIG. 3.

The parts 352 and parts 354 are assembled and their inner cavity filledby the hot solution described above by injection thru inlet 350 (notillustrated, but similar inlet 250 in FIG. 2. The solution was cooleddown in water bath and the injection inlet The resulting articlecomprising the PVC jacket (divisible to part 352 and part 354) and thesoft hydrogel inside are cooled to a -15° C. before use. After thehydrogel is frozen, the insert may be dipped briefly into warm water sothat a thin layer of gel beneath the PVC jacket melts. The parts 352 and354 are separated and the insert inserted into the rectum of thepatient.

Example 4

5 parts of rectal ointment, containing 3% of Liver Shark Oil; Live YeistCell Derivative, supplying 2000 units Skin Respiratory Factor per ounceof the ointment; and 0.01% of Phenylmercuric nitrate (Preparation H.Whitehall Laboratories Inc., N. York) were finely dispersed in 95 partsof the hot aqueous polymer solution from Example 3. The hot dispersionwas filled into the two-part mold/container from the Example 3 where itgelled to solid dispersion.

EXAMPLE 5

1 part of procaine hydrochloride and 1 part of phenylbutazone weredissolved in 98 parts of 1% aqueous polymer solution (the polymer is thepowerdered polymer described in the Example 3). The hot solution wasinjected into the mold/container 854 thru inlet 850, so that the wholespace 810 between the collar 830 and the PVC foil container was filledby the medicated hydrogel. Then the container was closed by weldinginlet 850.

We claim:
 1. A package means for treatment of rectal disordercomprisinga disposable substantially form retaining package ofpredetermined shape enveloping a water swellable polymer in gel formcomprising at least 35% by weight of water, said gel being selected toprovide an insert of sufficient rigidity to be inserted into the rectumafter said insert has been cooled to below 0° C. said insert, whenfrozen, comprising a substantially cylindrical body provided with asubstantially conical nose at one end thereof and a rearward collarproximate to the other end thereof, said nose facilitating insertion andsaid collar preventing initial total passage of the insert beyond thesphincter muscle of the rectum.
 2. A package means in accordance withclaim 1 additionally comprising a forward collar section located uponthe cyclindrical body rearwardly of the nose section and forwardly ofthe real collar, the forward face of said forward collar section havinga substantially frustro-conical cross-section and the rearward face ofsaid forward collar section lying in a plane substantially perpendicularto the longitudinal axis of the insert, whereby there is provided asubstantially cylindrical midsection between the rearward face of theforward collar and the forward face of said rear collar.
 3. A packagemeans in accordance with claim 1 wherein the rearward collar isdisplaced a sufficient distance forward of the rear end of the insert toenable the remaining rear portion to be finger held.
 4. A package meansin accordance with claim 3 wherein at least one portion of the curvedsurface of said rear most section is flattened to lie substantially in aplane substantially parallel to the longitudinal axis of the insert. 5.A package means in accordance with claim 2 wherein at least a portion ofsaid mid-section has a diameter less than the maximum diameter of thenose section of the insert.
 6. A device in accordance with claim 5wherein said mid-section has a diameter of between 50 and 25% of themaximum diameter of the nose section.
 7. A package means in accordancewith claim 2 wherein the diameter of the forward collar is between 150%and 250% of the maximum diameter of the nose section.
 8. A package meansin accordance with claim 1 wherein the gel comprises at least 90% water.9. A package means in accordance with claim 7 wherein the gel comprisesat least 98% by weight of water.
 10. A package means in accordance withclaim 8 wherein the device comprises a multi block copolymer ofacrylonitrile acrylamide having a water content of between 95 and 99.7%by weight.
 11. A package means in accordance with claim 1 additionallycomprising a pharmaceutically acceptable amount of a rectallyadministrable pharmaceutically active compound.
 12. A method of treatinghemorrhoids which comprises inserting into the rectum of a subjectafflicted therewith a substantially cylindrical insert shaped anddimensioned to enter readily thru the rectal sphincter muscle, saidinsert comprising a water swellable polymer having a water content of atleast 35% by weight, said insert having previously been frozen by beingsubjected to a temperature below 0° C. for a sufficient amount of timeto freeze the free water therein and maintaining said insert with atleast a portion thereof outside the sphincter muscle for at least oneminute.
 13. A method of claim 12 which comprises inserting into therectum of the subject affected by hemorrhoids a substantiallycylindrical device having a substantially conical nose end for insertionand a collar means having a diameter substantially greater than themaximum diameter of the nose portion located proximate to the rear endof the insert to prevent the passage of the entire insert through thesphincter muscle.
 14. A method in accordance with claim 12 wherein thedevice comprises at least 90% by weight of water.
 15. A method inaccordance with claim 14 wherein the insert comprises at least 98% byweight of water.
 16. A method in accordance with claim 12 wherein theinsert comprises a multiblock copolymer of acrylonitrile acrylamidehaving a water content of 95 to 99.7% of water.